Deoxo-fluor [bis(2-methoxy-ethyl)aminosulfur trifluoride]: An advanced nucleophilic fluorinating reagent in organic synthesis

Abstract

(A) Simple alcohols are readily converted into the corresponding monofluorides using Deoxo-Fluor™. Moderate to excellent yields were obtained with a variety of structurally diverse substrates, such as primary, secondary, tertiary, allylic and benzylic alcohols. For most of the compounds, fluorination proceeds below room temperature, sometimes as low as -78 °C. (B) Shreeve et al. found that when Deoxo-Fluor™ was reacted with various chiral amino alcohols, the corresponding chiral fluorinated compounds were produced in good yields. Under similar reaction conditions, diols reacted with Deoxo-Fluor™ to give good yields of the corresponding difluorinated products. (C) Rearrangement of 5-endo-methyl-6-exo-alcohols to 6-syn-methyl-5-anti-fluorides was initiated using Deoxo-Fluor™. (D) Reactions of structurally different aldehydes and ketones with Deoxo-Fluor™ have been utilized in order to prepare geminal difluoro compounds. The fluorination of aldehydes and ketones was conducted in the presence of catalytic amounts of HF, generated in situ, by adding trace amounts of EtOH to the reaction mixture. (E) A variety of thiocarbonyl derivatives (thioketone, thioester, thioamide, dithioester, and dithiocarbamate) were converted to the corresponding gem-difluorides in excellent yields on reaction with the fluorinating agent, Deoxo-Fluor™, in the presence of SbCl 3. (F) Shreeve and coworkers reported the reactions of various glyoxal hydrates with Deoxo-Fluor™. In concentrated solutions of dichloromethane, Deoxo-Fluor™ efficiently fluorinates a variety of glyoxal hydrates, RCOCHO·H2O (R = 4-methoxyphenyl, 3,4-methylenedioxyphenyl, 4-methylphenyl, 4-fluorophenyl, phenyl, 2-thienyl, methyl) to form polyfluoroethers as meso and racemic mixtures (∼1:1) in good yields. When the reactant comprised two different glyoxal hydrates, mixed polyfluoroethers were observed as the major products. (G) The Deoxo-Fluor™ reagent converts carboxylic acids to the corresponding acid fluorides, which then react with N,O-dimethyl-hydroxylamine to give the corresponding Weinreb amides in high yields. The reaction proceeds without racemization when optically active acids are used as starting material. This method is operationally simple and provides the products in high purity. (I) A mild and highly efficient cyclization of α-hydroxy amides (thioamides) to oxazolines (thiazolines) using the Deoxo-Fluor™ reagent has been developed. © Georg Thieme Verlag Stuttgart.